Quantitative and qualitative research suggests that urban disadvantaged environments may be highly stressful to their inhabitants. Social disorganization may be deleterious to both physical and mental health. The relationships among perceptions of one's neighborhood, measures of social support and social integration, and level of subsequent depressive symptoms was examined with a community sample of 818 individuals screened for an HIV prevention intervention, most of whom were current or former drug users. After adjusting for baseline levels of depressive symptoms, perceptions of neighborhood characteristics (vandalism, litter or trash, vacant housing, teenagers hanging out, burglary, drug selling, and robbery) predicted depressive symptoms at a 9-month follow-up interview. Measures of social support and social integration, entered as interactions with neighborhood perceptions, did not buffer the effect of neighborhood perceptions. However, CES-D scores at follow-up for frequent church attendees were lower. The data support theories of social disorganization and social stress and suggest the need for structural intervention.